Bupropion
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Bupropion: From Depression to Attention Deficit-Hyperactivity Disorder
One-Sentence Summary
Bupropion is a norepinephrine-dopamine reuptake inhibitor. Published reviews describe it as used for depression and smoking cessation (the license data supplied here do not state an approved indication). The TxGNN model predicts it may be effective for attention deficit-hyperactivity disorder (ADHD), with 8 registered trials (5 directly ADHD-related) and 20 publications on this direction, including one completed Phase 3 placebo-controlled trial and a Cochrane review.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the supplied license data. Reviews cite depression and smoking cessation. |
| Predicted New Indication | Attention deficit-hyperactivity disorder |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L2. The pack assigned L1, but L1 needs at least 2 completed Phase 3 RCTs and only one is confirmed (NCT00048360). |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data were not supplied. A 2023 review (PMID 37405312) describes bupropion as having no serotonergic activity and inhibiting the reuptake of norepinephrine and dopamine. These are the same catecholamine pathways targeted by established ADHD drugs. Stimulants such as methylphenidate and amphetamines increase dopamine and norepinephrine, and atomoxetine acts on norepinephrine.
Depression and ADHD often occur together, and adults with ADHD who cannot use or do not respond to stimulants need non-stimulant options. Reviews list bupropion among the non-stimulant choices (PMIDs 26601963, 38915262). The very high TxGNN score is consistent with this mechanism and with the existing clinical literature.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00048360 | Phase 3 | Completed | 162 | 8-week multicenter, randomized, double-blind, placebo-controlled, flexible-dose trial of extended-release bupropion (300-450 mg/day) in adults with ADHD. This is the main basis for the evidence level. The title is truncated, so the exact formulation should be confirmed. No results were supplied. |
| NCT00061087 | Phase 2/3 | Completed | 115 | Treatment of adult ADHD in methadone-maintained patients. The population is narrow and the drug arm is not confirmed from the title. |
| NCT00936299 | Phase 4 | Completed | 105 | Bupropion for ADHD in adolescents with substance use disorder. Direct bupropion-ADHD study in a comorbid population. |
| NCT01270555 | Not labeled | Completed | 32 | Open-label study of bupropion SR for ADHD in adults with recent or current substance use disorders. Small and uncontrolled. |
| NCT00000268 | Not labeled | Completed | 32 | Cocaine abuse with comorbid attention deficit disorder. Small; no results supplied. |
Three other registered trials were left out because they are not ADHD efficacy studies: smoking cessation (NCT03326128, terminated), stimulant-use relapse prevention (NCT04553263, withdrawn) and a CYP2B6 pharmacokinetic study (NCT00330434, withdrawn).
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28965364 | 2017 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Dedicated review of bupropion for adult ADHD, motivated by adults who do not respond to or tolerate psychostimulants. The abstract excerpt supplied has no results. |
| 27813651 | 2017 | Systematic review | J Child Adolesc Psychopharmacol | Bupropion in children and adolescents with ADHD, positioned as a promising non-stimulant alternative when stimulants fail or worsen comorbid conditions. |
| 30097390 | 2018 | Network meta-analysis | Lancet Psychiatry | Compares the efficacy and tolerability of oral ADHD medications across children, adolescents and adults. |
| 33085721 | 2020 | Network meta-analysis | PLoS One | Compares pharmacologic treatments for adult ADHD. |
| 38950507 | 2024 | Network meta-analysis | J Psychiatr Res | Bayesian network meta-analysis of monoamine reuptake inhibitors in ADHD, based on 31 clinical trials. |
| 40203844 | 2025 | Network meta-analysis (safety) | Lancet Psychiatry | Compares cardiovascular effects (haemodynamics, ECG) of ADHD medications. |
| 37405312 | 2023 | Review | Health Psychol Res | Bupropion pharmacology and use in depression, ADHD and smoking cessation. |
| 26601963 | 2016 | Review | Curr Pharm Des | Lists bupropion among common ADHD medications alongside stimulants and atomoxetine. |
| 38915262 | 2024 | Review | Expert Rev Neurother | Non-stimulant options for adults with ADHD who do not respond to or tolerate stimulants. |
| 26693882 | 2016 | Systematic review | Expert Rev Neurother | Alternative drug strategies for adult ADHD when methylphenidate and atomoxetine fall short. |
US Market Information
The supplied records list 20 authorizations and show the first 5 below. All are ANDA generics, and none includes approved-indication text.
| Authorization Number | Product Name | Dosage Form |
|---|---|---|
| ANDA210497 | Bupropion Hydrochloride (RemedyRepack) | Extended-release tablet |
| ANDA206122 | Bupropion Hydrochloride (ScieGen) | Film-coated extended-release tablet |
| ANDA090693 | Bupropion Hydrochloride (RemedyRepack) | Extended-release tablet |
| ANDA211347 | Bupropion Hydrochloride (Bryant Ranch Prepack) | Extended-release tablet |
| ANDA211020 | Bupropion Hydrochloride (Vangard Labs) | Extended-release tablet |
Oral tablets are the only route listed, in plain, film-coated and extended-release forms.
Safety Considerations
Package insert warnings, contraindications and interaction data were not available. Please refer to the package insert for safety information.
Two points from the supplied material are worth noting. The candidate notes state that bupropion lowers the seizure threshold. A 2025 network meta-analysis (PMID 40203844) compares the cardiovascular safety of ADHD drugs, and it should be reviewed before any use in ADHD.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The mechanism is plausible and the score is very high. One completed Phase 3 placebo-controlled trial, several smaller ADHD studies, and a Cochrane review with multiple network meta-analyses support it. Confirmed evidence does not reach L1, and the safety data are missing.
To proceed, the following is needed:
- Package insert warnings and contraindications, which are blocking for safety screening
- Mechanism-of-action data from DrugBank
- Confirmation of the formulation and the efficacy results of NCT00048360
- Confirmation of whether NCT00061087 was randomized and controlled, to decide between L1 and L2
- Review of the Cochrane and network meta-analysis results for bupropion’s effect size and tolerability versus stimulants and atomoxetine
- A seizure-risk and cardiovascular monitoring plan
- Attention to substance-use comorbidity, since most of the trials enrolled this population
Other predicted candidates: “ADHD, inattentive type” (rank 2) inherits the same rationale but has no subtype-specific trials (L4, research question). Ranks 3 to 10 have no plausible mechanism or no supporting evidence and should stay on Hold. “Obsolete hypertelorism” should be excluded from candidate lists.
This report is for research reference only and is not medical advice. Predicted indications require clinical validation before any use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.